Genetics and Progression of Early-onset Substance Dependence and HIV Risk

早发性物质依赖和艾滋病毒风险的遗传学和进展

• 批准号: 8693248
• 负责人: Christian J Hopfer
• 金额: $ 101.49万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-15 至 2019-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8693248
• 关键词: 14 year old; 18 year old; AIDS/HIV problem; ARHGEF5 gene; Address; Adolescence; Adolescent; Adult; Affect; Alcohol abuse; Alcohol or Other Drugs use; Amphetamines; Architecture; Behavior; Behavioral; Biological; Cessation of life; Characteristics; Cocaine; Cocaine Dependence; Cognition; Collaborations; Communities; Comorbidity; Complex; Conduct Disorder; Consultations; Criminal Justice; DNA; Data; Data Collection; Dependence; Development; Disease; Disinhibition; Dizygotic Twins; Drug Addiction; Enrollment; Environment; Environmental Risk Factor; Event; Exhibits; Family; Genetic; Genotype; Goals; HIV risk; Housing; Imprisonment; Individual; Joints; Life; Link; Longitudinal Studies; Marijuana; Measures; Methamphetamine dependence; Monozygotic Twinning; Monozygotic twins; Morbidity - disease rate; National Institute of Drug Abuse; Neurocognitive; Nicotine; Occupational; Opiate Addiction; Opiates; Parents; Participant; Pharmaceutical Preparations; Problem behavior; Public Health; Recruitment Activity; Reporting; Research; Resources; Risk Behaviors; Risk Factors; Role; Sampling; Severities; Sexual Partners; Siblings; Social Environment; Social support; Staging; Substance Addiction; Substance Use Disorder; Symptoms; Testing; Time; Twin Multiple Birth; Unsafe Sex; Work; Youth; addiction; anti social; base; comparative; critical developmental period; design; early onset; early onset substance use; family genetics; follow-up; genetic analysis; genetic epidemiology; high risk; high risk behavior; high risk sexual behavior; injection drug use; mortality; proband; psychosocial; public health relevance; self help; sex; substance abuse treatment; underage drinking; young adult

DESCRIPTION (provided by applicant): The research proposed in this application aims to understand genetic and environmental factors that promote desistance or continuation of problematic substance use and associated high-risk behaviors that began in adolescence. We propose an ~12-year follow-up (6 years after an initial 6-year follow-up) of an extremely affected adolescent sample as they transition into adulthood; this is a critical developmental period when we expect a portion of these individuals to decrease or desist problematic substance use and associated high-risk behaviors, while others will persist with the most serious, destructive behaviors leading to devastatingly high rates of morbidity and mortality. Our central goal is to understand the genetic and environmental factors that delineate these life trajectories. Results from our longitudinal research demonstrate that adolescent-onset substance users, who primarily exhibited abuse of and dependence on marijuana, nicotine, and alcohol during adolescence, progressed in the severity of their substance use five years later. As young adults, they report dramatically high rates of lifetime cocaine (29.2%), amphetamine (29.2%), and opiate (10.8%) use disorders as well as HIV/AIDS-related risk behaviors such as injection drug use (11%) and risky sexual behaviors. Indeed, when compared with community samples, these individuals report more than twice the number of lifetime sexual partners and a 33% higher rate of unprotected sex. Furthermore, they exhibit alarming rates of adult incarceration (55%) and early death (2.6%). This proposal extends our multiple-PI collaboration focused on the genetic epidemiology of adolescent-onset drug dependence. The three specific aims are to: 1) Identify distinct developmental trajectories of substance use, antisocial, and HIV risk behaviors in probands and siblings from adolescence to adulthood. a) Test initial characteristics of the adolescents, such as sex, severity of early onset substance use disorders (SUDs) and conduct disorder (CD), and neurocognitive functioning (e.g., disinhibition) that predict these trajectories and b) Test whether adult resources such as treatment for SUDs, housing stability, occupational stability, and social support are associated with these trajectories. 2) Determine the genetic and environmental architecture of developmental trajectories of substance use disorders, antisocial and HIV risk behaviors. a) Test the moderating role of social context, such as SES, criminal justice involvement, substance abuse treatment/self-help involvement, and stressful life events, in altering genetic influence and b) Test whether moderating effects vary across developmental periods (adolescence, young adulthood, and adulthood). 3) Test the influence of shared versus specific etiologic influences on measures of SUDs, antisocial behaviors, and HIV risk behaviors across development.

描述（由申请人提供）：本申请中提出的研究旨在了解遗传和环境因素，这些因素促进了青春期开始的问题物质使用和相关高风险行为的抑制或持续。我们建议对极度受影响的青少年样本进行约12年的随访（最初的6年随访后的6年），直到他们过渡到成年；这是一个关键的发展时期，我们期望这些人中的一部分减少或停止使用有问题的物质和相关的高风险行为，而其他人则会坚持最严重的，破坏性的行为，导致毁灭性的高发病率和死亡率。我们的中心目标是了解描述这些生命轨迹的遗传和环境因素。我们的纵向研究结果表明，青春期开始的物质使用者，在青春期主要表现出对大麻、尼古丁和酒精的滥用和依赖，五年后他们的物质使用的严重程度有所提高。作为年轻人，他们报告的终生可卡因（29.2%）、安非他明（29.2%）和阿片类药物（10.8%）使用障碍以及与艾滋病毒/艾滋病相关的危险行为，如注射吸毒（11%）和危险的性行为的比例非常高。事实上，与社区样本相比，这些人报告的终生性伴侣数量是社区样本的两倍多，无保护性行为的比例高出33%。此外，这些国家的成人监禁率（55%）和早逝率（2.6%）令人震惊。该建议扩展了我们的多pi合作，重点是青少年发病药物依赖的遗传流行病学。三个具体目标是：1)确定先证者和兄弟姐妹从青春期到成年的物质使用、反社会和艾滋病毒风险行为的不同发展轨迹。a)测试青少年的初始特征，如性别、早发性物质使用障碍（sud）和品行障碍（CD）的严重程度，以及预测这些轨迹的神经认知功能（如去抑制）